SQ22536 and W-7 inhibit forskolin-induced cAMP elevation but not relaxation in newborn ovine pulmonary veins

Eur J Pharmacol. 2001 Apr 20;418(1-2):111-6. doi: 10.1016/s0014-2999(01)00929-3.

Abstract

The role of cAMP in forskolin-induced relaxation was studied in isolated pulmonary veins of newborn lambs (7-12 days). In vessels preconstricted with endothelin-1, forskolin at concentrations < or =10(-7) M had no effect on cAMP content and adenylyl cyclase activity but caused up to 50% relaxation. At higher concentrations, forskolin markedly elevated cAMP content and adenylyl cyclase activity and caused a further relaxation. SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine; an adenylyl cyclase inhibitor] and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide; a calmodulin-dependent adenylyl cyclase inhibitor] had no significant effect on forskolin-induced relaxation but markedly inhibited the elevation of cAMP content and adenylyl cyclase activity caused by forskolin. Rp-8-CPT-cAMPS [8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate; an inhibitor of cAMP-dependent protein kinases] and Rp-8-Br-PET-cGMPS (beta-phenyl-1, N(2)-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate; an inhibitor of cGMP-dependent protein kinases) attenuated the relaxation caused by a cAMP analog but not that caused by forskolin. These results suggest that cAMP may not play a major role in forskolin-induced relaxation of pulmonary veins of newborn lambs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / metabolism
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenine / analogs & derivatives*
  • Adenine / pharmacology*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Animals, Newborn
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Colforsin / antagonists & inhibitors*
  • Colforsin / pharmacology
  • Cyclic AMP / biosynthesis
  • Cyclic AMP / metabolism*
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Endothelin-1 / pharmacology
  • Enzyme Induction / drug effects
  • Female
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Pulmonary Veins / cytology
  • Pulmonary Veins / drug effects*
  • Pulmonary Veins / metabolism*
  • Pulmonary Veins / physiology
  • Sheep / physiology*
  • Sulfonamides / pharmacology*
  • Thionucleotides / pharmacology
  • Time Factors
  • Vasodilation / drug effects

Substances

  • Endothelin-1
  • Sulfonamides
  • Thionucleotides
  • 8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate
  • 9-(tetrahydro-2-furyl)-adenine
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • W 7
  • Cyclic AMP
  • Adenylyl Cyclases
  • Cyclic GMP
  • Adenine